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An amyloid is a deposit of fragments found in many organs derived from breakdown (proteolysis ) of a larger precursor protein. In the case of serum amyloid, the protein component is an immunoglobulin. When the amyloid deposition causes disease it is often due to a mutation in the precursor protein causing abnormal proteolytic processing (Primary amyloidosis). This is seen in familial Alzheimer’s disease and in hereditary cerebral haemorrhage with amyloidosis of Dutch type (HCHWA-D). The amyloid deposition is the result of other disease in secondary amyloidosis, as in sporadic Alzheimer Disease.
Neurofibillary tangles are amyloid, however, the term amyloid is retained for description of deposits of B-amyloid in plaque cores outside the cells and in blood vessels and to use Neurofibillary tangles to describe the intraneuronal protein deposits which are, nevertheless, an amyloid according to their histochemical staining properties. and PHF Amyloid deposits are also found in normal old age, Down’s syndrome, ALS-Parkinsonism-Dementia complex of Guam (diffuse plaques), Dementia pugilistica (diffuse plaques), Hereditary cerebral haemonhage with amyloidosis of Dutch type (HCHWA-D) (vascular) and Sporadic cerebral angiopathy (vascular).
Scrapie -type plaques are different from Alzheimer Disease senile plaques and they are found in the spongiform encephalopathies or prion diseases: which include Creuttfeldt-Jakob disease (CJD), Kuru, Gerstmarin-Straussler-Scheinken syndrome (GSS), Scrapie, and Bovine spongiform encephalopathy (BSE).
Aluminium is implicated in plaque formation. Edwardson and colleagues isolated plaque cores stripped of protein and they found that the remainder of the core is inorganic – Aluminium, and Silicon. Earlier studies claimed that tangle-bearing neurones in Alzheimer Disease and ALS-Parkinsonism-Dementia complex of Guam also contain elevated levels of Aluminium. Aluminium is neurotoxic (e.g. dialysis encephalopathy), but most Aluminium is excreted and very little crosses the blood brain barrier. In plasma Aluminium is bound to transferrin and accumulates in rat brain in areas with highest levels of transferrin receptors. Epidemiological studies have reported a small increased risk of dementia in geographical areas with high Aluminium in drinking water – these studies are greatly criticised.
Amyloid isolated from meningeal blood vessels in brains affected by Alzheimer disease is called B-protein or A4-protein or AB. The deposit is filamentous and insoluble forming diffuse plaques. Diffuse plaques occur in the cerebellum as well as widely distributed throughout other areas of brain. Many intellectually intact brains have abundant diffuse plaques. Diffuse plaques are probably not damaging to the brain and are often presumed to be precursors of the classical plaque – but this is not proven. Down’s syndrome brains at around age 20 years have diffuse deposits but no neuritic involvement nor Neurofibillary tangles. Thus, AB deposition is taken to be first manifestation of AD pathology.
The amyloidal precursor protein (APP) gene is located on chromosome 21. APP is a member of a family of homologous proteins. In the brain, APP is made mainly found in neurones. It has been suggested that the formation of the AB and hence amyloid deposits may result from an imbalance in the proportion of APP forms expressed in the brain. Down’s cases develop amyloid deposits in their twenties. Down’s patients have an extra copy of APP gene on the third copy of chromosome 21; this leads to elevated expression of APP and Down’s syndrome patients after age 35 have a pathology indistinguishable from AD.